Antibody Isotype Switching As a Mechanism to Counter HIV Neutralization Escape

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2020 Nov 25

PMID 33238131

Citations 14

Authors

Cathrine Scheepers

Valerie Bekker

Colin Anthony

Simone I Richardson

Brent Oosthuysen

Thandeka Moyo

Prudence Kgagudi

Dale Kitchin

Molati Nonyane

Talita York

Dieter Mielke

Batsirai M Mabvakure

Zizhang Sheng

Bronwen E Lambson

Arshad Ismail

Nigel J Garrett

Salim S Abdool Karim

Lawrence Shapiro

Carolyn Williamson

Lynn Morris

Penny L Moore

Affiliations

Soon will be listed here.

Abstract

Neutralizing antibodies (nAbs) to highly variable viral pathogens show remarkable diversification during infection, resulting in an "arms race" between virus and host. Studies of nAb lineages have shown how somatic hypermutation (SHM) in immunoglobulin (Ig)-variable regions enables maturing antibodies to neutralize emerging viral escape variants. However, the Ig-constant region (which determines isotype) can also influence epitope recognition. Here, we use longitudinal deep sequencing of an HIV-directed nAb lineage, CAP88-CH06, and identify several co-circulating isotypes (IgG3, IgG1, IgA1, IgG2, and IgA2), some of which share identical variable regions. First, we show that IgG3 and IgA1 isotypes are better able to neutralize longitudinal autologous viruses and epitope mutants than can IgG1. Second, detrimental class-switch recombination (CSR) events that resulted in reduced neutralization can be rescued by further CSR, which we term "switch redemption." Thus, CSR represents an additional immunological mechanism to counter viral escape from HIV-specific antibody responses.

Citing Articles

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Moysi E, Sharma A, ODell S, Georgakis S, Del Rio Estrada P, Torres-Ruiz F bioRxiv. 2024; .

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